Email From Dr. Costantini June 14, 2018

Dr. Costantini sent this yesterday regarding Levodopa and Thiamine and their synergy together, but it was not translated correctly so I sent it back to him and he corrected it. This is his revised version:

Dear Art,

The doses of levodopa taken by the patients who write to me are very low. This (I think) is because there is still fear of levodopa that is totally unjustified. This could affect the results obtained by adding the necessary doses of levodopa to thiamine. Thiamine is healing and stops the disease progress, in our experience. The levodopa best used by the recovered cells can bring the amount of dopamine in the brain to the level necessary to significantly improve almost all symptoms.

The onset of motor complications is independent of the duration of levodopa therapy but closely linked to the natural progression of the disease (see the following article).

In our patients who started thiamine treatment, even after 10 years of levodopa treatment, with the addition of thiamine, no symptoms related to late complications of levodopa have ever occurred. Thiamine is effective in reducing the intensity of late complications from levodopa. These data support the hypothesis that thiamine has a restorative and neuroprotective action in Parkinson's disease .

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Brain. 2014 Oct;137(Pt 10):2731-42. doi: 10.1093/brain/awu195. Epub 2014 Jul 17

The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa.

Cilia R1, Akpalu A2, Sarfo FS3, Cham M4, Amboni M5, Cereda E6, Fabbri M7, Adjei P2, Akassi J3, Bonetti A8, Pezzoli G8.

Author information

Abstract

During the past decade, a number of large drug trials suggested that the initiation of levodopa therapy should be delayed to reduce the risk of motor complications in patients with Parkinson's disease. However, the relative contribution of the cumulative exposure to levodopa and of disease progression to the pathophysiology of motor fluctuations and dyskinesias is still poorly understood. In this 4-year multicentre study, we investigated a large cohort of patients with Parkinson's disease in a sub-Saharan African country (Ghana), where access to medication is limited and the initiation of levodopa therapy often occurs many years after onset. The primary objective was to investigate whether the occurrence of motor complications is primarily related to the duration of levodopa therapy or to disease-related factors. Study design included a cross-sectional case-control analysis of data collected between December 2008 and November 2012, and a prospective study of patients followed-up for at least 6 months after the initiation of levodopa therapy. Ninety-one patients fulfilled criteria for clinical diagnosis of idiopathic Parkinson's disease (58 males, mean age at onset 60.6 ± 11.3 years). Demographic data were compared to those of 2282 consecutive Italian patients recruited during the same period, whereas nested matched subgroups were used to compare clinical variables. Demographic features, frequency and severity of motor and non-motor symptoms were comparable between the two populations, with the only exception of more frequent tremor-dominant presentation in Ghana. At baseline, the proportion of Ghanaian patients with motor fluctuations and dyskinesias was 56% and 14%, respectively. Although levodopa therapy was introduced later in Ghana (mean disease duration 4.2 ± 2.8 versus 2.4 ± 2.1 years, P < 0.001), disease duration at the occurrence of motor fluctuations and dyskinesias was similar in the two populations. In multivariate analysis, disease duration and levodopa daily dose (mg/kg of body weight) were associated with motor complications, while the disease duration at the initiation of levodopa was not. Prospective follow-up for a mean of 2.6 ± 1.3 years of a subgroup of 21 patients who were drug-naïve at baseline [median disease duration 4.5 (interquartile range, 2.3-5) years] revealed that the median time to development of motor fluctuations and dyskinesias after initiation of levodopa therapy was 6 months. We conclude that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy, but rather with longer disease duration and higher levodopadaily dose. Hence, the practice to withhold levodopa therapy with the objective of delaying the occurrence of motor complications is not justified.

KEYWORDS:

Parkinson’s disease; dyskinesias; levodopa; pathophysiology

Comment in

•'Don't delay, start today': delaying levodopa does not delay motor complications. [Brain. 2014]

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Best regards,

Antonio Costantini

[Hidden]

Thiamine is healing and stops the disease progress, in my experience.

[hanifab23 in reply to Hidden]

RoyProp

Please tell me website you order the capsules from

and the name

[Hidden in reply to hanifab23]

Vitacost.com

Vitacost vitamin B1 (as thiamin HCI) 500mg, easy swallow capsules

[ryanJames1]

Mmm still not convinced happy to be still med free the whole on/off bother s me I am just the same all day

I guess time will tell

[gingerj in reply to ryanJames1]

I would have agreed with you until this past week. I have been diagnosed 2 years. Only started sinemet this week. One 62.5 mg a day. Just to see if I noticed any difference. I can tell. Less stiffness and pain for a few hours. Not sure if it improves the tremor.

[ryanJames1 in reply to gingerj]

Hi Gingerj

Glad you are getting relief

I have found mannitol and the thiamine have done the same for me

Mine is only a personal opinion as I am tremor dominant I don't see any value in meds for me and hopefully the thiamine will continue to work alleviating some of the other symptoms

[Grumpy77 in reply to ryanJames1]

hello Ryan,

where do you buy your mannitol from?

[ryanJames1 in reply to Grumpy77]

blackburndistributions.com/

I have found cost is about $80 for 1kilo I live in Australia no one in US ships to here

Let me know how you go

[aliciamq in reply to gingerj]

What about adding amantadine/symetrel? I understand they work together for something~

[dadcor]

OK, I just wonder if these 'safety" statements apply for the usage of the combination Carbi or Benzerazide-Levodopa together with thiamine or just for the Levodopa alone together with thiamine..

[Kia17 in reply to dadcor]

dadcor

Dr Costantini usualy referring Sinemet as Levodopa

[aliciamq in reply to Kia17]

Sinemet is carbidopa and levadopa - my understanding of it ~

[caroldelaune]

I thought the problem was the combination of carbodopa/levodopa...not levodopa alone.

[Despe]

What about patients not on C/L yet? Would just Thiamine suffice? My husband started MP last Friday. Neurologist at Mayo said no meds yet, 1-2 years down the road.

I did email Dr. C and gave him all the information he wanted.

[Hidden]

I just wrote this to Dr. Costantini :

Dear Dr. Costantini,

Some members on the HU forum are asking a question about your recent email about Levodopa and thiamine.

The members seem to agree that levodopa is not the problem as you stated in your email, but they feel the problem is the carbidopa that is often included with their levodopa prescription as both in one capsule. I believe the product is called Sinemet that has the levodopa and carbidopa together.

The question then, if you take carbidopa / levodopa (as Sinemet) will the thiamine still prevent late stage development of problems like dyskinesia?

Thank you very much as always!

Art

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This is is the reply he just sent:

Certainly. Yes

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I will add this to the Thiamine FAQ page as question and answer number 39.

Art

[jujulini in reply to Hidden]

but, if we are already experiencing them, will it help to lesson or eliminate them?

[Hidden in reply to jujulini]

According to Dr. Costantini, yes.

Art

[Juliegrace in reply to jujulini]

I believe it made my dyskinesia worse. I took injections for 4-1/2 months and gradually my dyskinesia got worse without any increase in my meds. I stopped the injections (on the advice of Dr. C) and within days my dyskinesia had lessened. I waited 15 days and tried oral HCl, but on 500 mg for one day, I did not feel well. The next day I tried 1000 mg and my dyskinesia increased. It lessened again after I stopped. Then, after contacting Dr. C again I started 100mg of allithiamine daily. I had taken it for 30 days before I started the injections. I stopped after four days because I just did not feel good.

I filled a prescription for amantadine right before I stopped the injections because I was feeling desperate to lessen the dyskinesia, which had become exhausting. I haven't taken any yet because the dyskinesia is much more tolerable since I stopped taking the thiamine.

[Hidden in reply to Juliegrace]

Juliegrace,

Can you copy your post to this page about people who are currently taking thiamine?

healthunlocked.com/parkinso...

Thank you.

Art

[jujulini in reply to Juliegrace]

try the amantadine. it helped my dyskinesias and no ill effects noted. i take 300mg/day - at breakfast, lunch, and then at 4:00. i dont want to take it later, because it can cause insomnia, and i already have that problem. i started oral thiamine 3gm/day per dr costantinis recommendation, and i didnt feel right. i waited a couple of days, and started it up again at 2gm/day. this is the 2nd day, so the verdict is still out. i am going to post my experience with thiamine, once i give it a little more time. thanks for posting yours.

[dadcor in reply to Hidden]

Thanks Art !!

[dadcor in reply to Hidden]

Hi Art, may be another question for Dr C: When the pull test should be performed, before or after taking the Ldopa dose? Anyway when you take your Ldopa dose and it kicks in, you feel better..

[Hidden in reply to dadcor]

Hi dadcor,

I recently sent a new list of questions to Dr. Costantini and your question is already in that list! I will add them to the thiamine protocol FAQ page as soon as he sends them back.

Regarding your particular question, I would think it would be important that it would be the same at each test, either always on or always off, but Dr. Costantini will clarify, I'm sure!

Art

[jujulini in reply to Hidden]

i had asked dr c if the pull test should be done whe "on" or "off", and he said "on".

[Gioc in reply to dadcor]

I'm not an expert, but since it's about balance it's perhaps a no-motor symptom that in my opinion is not influenced by l-dopa, but I might be mistaken. Gio

[Juliegrace]

Below is what Dr. Colangeli wrote in the post by KIA17 about thiamine and dyskinesia (link to post provided below). I do not recall reading anything from Dr. C saying that thiamine will eliminate dyskinesia in those that already suffer from it.

"Dear Kia,

I have consulted with Dr Costantini about your query and I do confirm that on the basis of our observations: our patients who do use l-dopa in addition to thiamine have not developed dyskinesia. This is true for patients who are under treatment for 3 to 5 years (we invented this treatment in 2013). However, you should inform Dr Costantini or myself about your current l-dopa regime and he will see if it needs to be adjusted.

We do consider the timeframe above “long term” but further studies are necessary to confirm that patients will be dyskinesia-free lifelong though we are optimistic.

Thank you for your patience,

Best regards

-Marco"

healthunlocked.com/parkinso...

[whatadrama]

I understood that carbidopa not levadopa can cause dyskonesia...sinimet has both. The c helps the l to do a better job ( simply put) according to specialists. Mucuna pruriens which is natural l -dopa ...seems to be well absorbed without the added carbidopa. Studies have been done and dyskonesia ( which is head/body swaying movement..... not shaking) they say I'd CAUSED in time by CARBIDOPA...

[bassofspades in reply to whatadrama]

According to dr marty hinz, and you can take it or leave it, carbidopa is added to levadopa to reduce nausea. This is because a smaller dose of levadopa is required since carbidopa prevents peripheral metabolism of levadopa and more will be available for the brain. But, Hinz states, carbidopa binds irreversibly to b6 receptors which causes said dyskinesia. Like i said, take it or leave it. Dr Costantini says if we stick with b1 we will not get dyskinesia either with levadopa or sinemet (which contains carbidopa) so thats very good news.

Some think these guys are kooks but most find their work very helpful. I know it helps me.

[Tryguy in reply to bassofspades]

Hey bass of spades, It looks like the Hinz formula is working or you. Have the dosages been pretty stable? After over a year of no results with Hinz, I switched to C/L WITH a supplement of Mucuna. This has given my life back again. So, the Hinz protocol gave me this idea (originally using the D5), BUT there is still a Carbidopa component, which I would still like to eliminate. Have you tried the thiamine?

[bassofspades in reply to Tryguy]

Yes i am on thiamine since feb 1 2018. Instead of carbidopa, i use egcg, which has a similar effect. So essentially, mucuna plus egcg equals c/L. I think! I have been trying to cut my night time dose of mucuna and cysteine out as of 2 days ago. So far so good! My regimen is as follows...

8am - 1.5 g b1

12 pm - 1.5g b1, 2 d5 (mucuna), 1 neuro replete(5htp plus cofactors), 2 cystreplete, 200mg egcg

4 pm - 2 d5, 1 neuro replete, 2 cystreplete, 200 mg egcg.

8pm (trying to eliminate ) 2 d5, 2 cystreplete.

I am always tweaking my supplements but my hinz protocol has been the same since day one, july 2017. No "Off times", although symptoms were more pronounced in the morning. Since adding thiamine i have been getting better and better in every way.

Do you stilll use neuroreplete and cystreplete with c/L? I would think that would be a good combo, and of course, with thiamine!

[ryanJames1 in reply to bassofspades]

Hi bassofspades

What brand of egcg do you buy

[bassofspades in reply to ryanJames1]

Honestly whatever's cheapest! Right now its Now brand.

[ryanJames1 in reply to bassofspades]

Ok thank you 😊 Wasn't sure if you tried to make it organic or not

[bassofspades in reply to ryanJames1]

Not a bad idea!

[ryanJames1 in reply to bassofspades]

Yes it seems most comes from India or China I can't find any usda organic that would ship to Oz

[bassofspades in reply to ryanJames1]

"Oz"? is that somewhere over the rainbow? Where are you located?

[Hidden in reply to bassofspades]

Nickname for Australia.

Art

[bassofspades in reply to Hidden]

I was gonna guess that. Thanks!

[ryanJames1 in reply to bassofspades]

Yes over the rainbow and down a bit lol!!

Oz is Aussie slang for Australia

[bassofspades in reply to ryanJames1]

I splurged and bought the organic coconut oil yesterday. Wow its expensive!

[ryanJames1 in reply to bassofspades]

Yes it is but better to rotate organic options if we can't afford them all the time than possibly do more harm with unknown contaminates

I always buy usda organic Mucuna I haven't had any coconut oil for a while so must splurge again when I do buy it I try to get cold pressed organic

By cold pressed it means no chemicals have been used to extract the oil

[bassofspades in reply to ryanJames1]

We are worth it!

[JANVAN in reply to bassofspades]

Hi bassofspades !

And are you still fulltime working ? At the "radiology"?

I keep on fighting but getting worse the last weeks (rigidity-periods, of course a lot of stress in the job and the last weeks very hot for Europe).

I'm on 3 times 25/100 Sinemet, and I will be careful to decrease that dosis, but I want to !!!

Been to Dr. Costantini in Rome, just the time of his visitation I had I very good moment...., so he was a bit thinking why do you come already.....

He proposed to do injections of 50 ml Thiamine once a week....no doing that for two weeks...., still have to wait a bit, I think ??

I'm also on the Coimbra-Protokoll, but now I'm a bit doubting, because no one seems to use it here

(synergetic with Dr. Costantini, they recommend also a lot of Mg.....)......

Hopefully greetings!

JANVAN

[bassofspades in reply to JANVAN]

Why wait?

Im still working and working a lot. Ive been doing really good! Taking my thiamin, my aminos and my whey protein. Feeling like im firing on almost all of my cylinders!

[Erniediaz1018 in reply to bassofspades]

If you're in the state's buy from WalMart or even cheaper Aldis

[dadcor in reply to bassofspades]

HI, would you pls update on your protocol..? Were you able to cut some dose..?

[bassofspades in reply to dadcor]

for thiamine, my dose remains at 3000mg per day. 4000 was too much and stopped working. 2000 did nothing for me.

[GalinaBlanca in reply to bassofspades]

Dear Bassofspades, could you specify how much mucuna do to get per doze and what milligrams? I bough for my father mucuna 400 mg and each pill contains 15% levodopa! We would like to try with it but we don’t know the doze. Tanks!

[bassofspades in reply to GalinaBlanca]

Everybody's dose is going to be different, depending on a bunch of factors. Severity of disease, metabolic factors, co factors, synergies of meds and supplements and on and on.

My personal dose is 3x a day, 2 pills of 166mg mucuna that equal 100mg each L Dopa. Is he on any meds now?

[GalinaBlanca in reply to bassofspades]

Thanks for the answer! He is on madopar which contains levodopa and Benzerazid. He is on an average doze. I guess if he replaces one of the takes with mucuna he should also take egcg to avoid dyskinesia from what I read here. The problem is there are no doctor willing to try alternative ways and we have to check by ourselves. Thanks God there are people like you willing to share this!

[bassofspades in reply to GalinaBlanca]

Egcg sounds like a good idea. I estimate the ratio of levadopa from madopar is 4:1, so 25mg levadopa content in madopar probably converts to 100mg levodopa in mucuna. 200mg egcg is what i used to use. Now with everyone taking b1 there shouldn't be any dyskinesia issues at all. Please dont just take my advice willy nilly, seek a professional opinion! Good luck!

[GalinaBlanca in reply to bassofspades]

Thanks again! B1 is thiamin, right?

[bassofspades in reply to GalinaBlanca]

Yes

[bassofspades in reply to GalinaBlanca]

m.pdr.net/Mobile/Pages/drug...

If you read this carefully under the dosing tab, it might give you a clue on how to convert dosage from c/l (sinemet) to levadopa. Some math is involved as well as experimentation. I would seek a physician's advice to be safe!

[Juliegrace in reply to whatadrama]

I have experienced dyskinesia from MP (98% pure l-dopa) at a dose less than 100mg.

[bassofspades in reply to Juliegrace]

A lot of people have trouble with the pure stuff. Maybe too much gets metabolized peripherally too quickly?

[Juliegrace in reply to bassofspades]

I agree, but my point was this levodopa without carbidopa can cause dyskinesia.

[bassofspades in reply to Juliegrace]

Maybe try 200mg egcg with your mucuna?

[Erniediaz1018 in reply to Juliegrace]

Me too

[Tryguy]

Has there been any discussion of A) recommended dosages of thiamine AND B) whether Benfotiamine works (a more ‘readily absorbable’ version of Thiamine)

Thanks!

Tryguy

[GalinaBlanca]

Has anyone tried the transdermal patches with levodopa?